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DOI: 10.1055/s-0031-1274049
Deficiency of the mitochondrial phosphate carrier as a cause of combined mitochondrial (cardio-)myopathy
The mitochondrial phosphate carrier is an essential enzyme of mitochondrial ATP synthesis. The enzyme is expressed in two tissue-specific isoforms by mutually exclusive alternative splicing of the SLC25A3 gene transcript. A first phosphate carrier defect was described recently as a novel defect of oxidative phosphorylation.
Here we describe a second family with 3 affected children from consanguineous parents presenting with neonatal onset hypertrophic cardiomyopathy and generalised muscular hypotonia and normal mental development. Lactate was constantly elevated. One of the patients died in infancy, the course of the two surviving patients is not progressive with persisting hypertrophic cardiomyopathy and muscular atrophy, the oldest is 17 years now.
In a muscle biopsy the respiratory chain enzymes including oligomycin sensitive ATPase were normal. In the further diagnostic workup we identified a homozygous intronic mutation c.158–9A>G in the SLC25A3 gene located at the 5'-intronic side of the heart and skeletal muscle specific exon 3A. This mutation creates a novel splice acceptor site, resulting in an insertion of 8 base pairs in the mRNA. The splicing at the wild type splice site was decreased more than 95%.
In conclusion, in patients with (cardio-)myopathy and constantly elevated lactate, a defect of the mitochondrial phosphate carrier has to be considered, especially when respiratory chain enzymes are normal.